Cue Biopharma, Inc.

Good morning and welcome to the QBioPharma's novel biologics portfolio. At this time, all attendees are in a listen-only mode. Today's call will focus on a review of Q's novel biologics development platform for immobilizing the immune system. Joining me on today's call is QBioPharma's chief executive officer, Dan Passari, two recognized T-cell researchers, Dr. Richard DiPaolo and Dr. Andy Cope, and members of Q Management. Please note that this presentation and discussion is being recorded and will be available in the Investors and Media section of the company's website at qbiopharma.com for the next 30 days. Additionally, some of the statements we make on this call will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results could differ materially from those stated or implied by these forward-looking statements due to important risks and uncertainties associated with the company's business, including those set forth in the risk factors and in management's discussion and analysis of financial condition and results of operations section of QBioPharma's Annual report on Form 10-K for the year ended December 31, 2024, filed on March 31, 2025. It's quarterly report on Form 10-Q filed on May 12, 2025, and any other filings that we may make with the SEC. In addition, any forward-looking statements represent our views as of today, May 15, 2025. Q undertakes no obligation to revise or update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments, or otherwise, after the date of this conference call. Now, I would like to hand the call over to Q's CEO, Dan Passeri. Dan?

Thank you, Tara, and good morning, everyone. Welcome to QBioPharm's Novel Biologics Portfolio Event. The agenda for today's call is shown here on slide four, with the primary focus of today's call being that we're going to provide an update and convey what we believe to be the tremendous potential of Q401 for addressing autoimmune and inflammatory diseases. And we also have two immunology key opinion leaders joining us on today's call. I'll first begin with a summary of QBioPharmers' unique and highly differentiated biologics platform, and we'll also provide a brief update from our Q100 oncology series. I'm then going to turn the call over to Dr. Matteo Levassetti, our chief medical officer, to introduce the importance of regulatory T cells and the pioneering protein engineering that went into designing Q401 as a first-in-class TGF-beta and IL-2 bispecific to enable the induction of stable and durable regulatory T cells or Tregs. Following Matteo's introduction to Q401, Dr. Rich DiPaolo, a pioneer in regulatory T-cells, will share his perspective on Q401's mechanism of action for generating Tregs, including in vivo data generated from his lab in an autoimmune gastritis disease model. And TAO will then return to present additional data demonstrating not only proliferation of already existing NT regs, but also the induction of new T regs from effector T cells. These are referred to as IT regs, which is a key differentiator and what we believe represents a major breakthrough development. Matteo will present data for Treg induction and proliferation and several additional autoimmune disease models further supporting the premise that Q401 is the first in class disruptive therapeutic representing a potential new standard of care with broad application across autoimmune disease and inflammatory disease. Following Matteo, Dr. Andy Cope will share his perspective as a renowned academic practicing rheumatologist and immunologist on the potential of Q401 to change the treatment paradigm for patients suffering with autoimmune disease. We'll then wrap up with a question and answer session, including Dr. Cope and members of the Q management team. I'll then come back to conclude with a few closing statements. As detailed on slide five, I'm going to begin by sharing a high level summary of the key takeaways of our Immunostat platform and various programs under development. It's recognized and understood that the immune system protects us from serious diseases through selective activation of specific T cell and B cell populations. An imbalance in these populations can lead to serious diseases such as autoimmune disease and cancer. And we believe our biologics platform has the potential to restore proper immune balance for the treatment of these serious diseases. We aim to achieve this with our engineered biologics that are designed to mobilize selected T cell populations by mimicking nature's key regulatory mechanisms or cues, hence the company's name. We believe that Q401 holds tremendous potential to become a new standard of care for treating autoimmune and inflammatory diseases representing major markets of unmet medical need. And the data we'll share today aims to further support this premise. We recently announced a collaboration with Berger Engelheim for the development of Q501 for targeting and depleting B cells implicated in B cell mediated autoimmune disease, providing independent positive validation of the Q500 series, which harnesses the potential of the body's intrinsic antiviral killer T cells to treat autoimmune disease as well as cancer. To learn more about this program, please listen to our webcast located on our website that we had during April. And I'll now provide a brief update on our oncology programs, which have provided the foundational basis for the engineering and design of our other programs from our platform. The maturing clinical data from our oncology programs continues to demonstrate highly encouraging metrics of clinical benefit and tolerability. Three patients remain on treatment with Q101 in the frontline setting of recurrent or metastatic HPV-positive head and neck squamous cell carcinoma in combination with the standard of care pembrolizumab, also known as Keytruda. In the second, I'm sorry, the monotherapy trial in a second line setting and beyond, as shown here on slide six, We have observed in heavily pretreated patients, notable survival benefit in those treated with Q101. In this setting, we observed a highly encouraging median overall survival of greater than 20 months. And that's compared with the historically reported median overall survival of approximately eight months observed in the second line trials that were historically reported for NIVO and PEMBRO. Importantly, in the graph on the left panel, notable survival was observed at the higher active dose levels of Q101, supporting its proposed mechanism of action. So in the absence of a comparator in this study, the low dose population, which is in essence inactive, serves as an internal control. All patients received the same prior and various follow-on anti-cancer treatment with the only variable being whether they were treated with the high active dose or the lower doses, which we haven't seen clinical activity at those lower doses of Q101. We believe the clinical activity and enhanced survival observed in this trial is due to the repeated stimulation and expansion of tumor-specific T cells, given the mechanism of action of Q101. The culmination of data positions us well for pursuing strategic alternatives, including prospective partnering options for these assets, and we look forward to giving you updates in the future. The Q100 series importantly has been foundational to the evolution of our platform, including the Q500 series and Q401. And what I mean by that is that various key functional components of the 100 series have been deliberately incorporated into these subsequent programs to enable specific mechanistic properties in these molecules. Now, pertaining to our Q500 series, here on slide 7 is a synopsis of the recently announced partnership with Berger Engelheim for Q501. The Q500 series, including Q501, is designed to bind specific pathogenic cells and present a defined viral epitope, such as CMV, thereby harnessing the patient's intrinsic antiviral killer T cells that are circulating through their blood to attack and destroy the targeted cell that basically has been painted with that viral protein. Our partnership with BI for targeting and depleting B cells represents both a validation and acceleration for the development of Q501, as well as providing Q with non-dilutive capital. Importantly, we retain the rights to all applications of the Q500 series outside of B-cell targeting and depletion. As you can see on slide eight, from left to right, each distinct series uses a different combination of molecular components, each designed to confer specific mechanistic properties for the treatment of cancer as well as autoimmune disease. For example, The modified IL-2 from the Q100 series has been specifically engineered to bias towards conditional binding, which has also been incorporated into Q401, which is a bispecific that conditionally binds to TGF fader and IL-2 receptors. And Matteo will elaborate upon this momentarily. I'm now going to turn the call over to Dr. Matteo Levesetti, our chief medical officer. to review the data from our Q401 program and to describe what we believe represents a promising and unprecedented opportunity to establish a new standard of care for the treatment of autoimmune and inflammatory disease. Matteo? Thank you, Dan.

Good morning, everyone. Autoimmune disease is generally driven by a set of inflammatory cells called T lymphocytes. From a simplified perspective, T lymphocytes come in two types. The first type is referred to as effector T cells, which are responsible for inducing inflammatory responses that protect us from infections or cancer. The second type of cells referred to as regulatory T cells or Tregs are powerful anti-inflammatory cells that control the immune activity of effector T cells, preventing inflammatory responses from going too far and causing damage to cell. Tregs control T effectors by several mechanisms, including secreting multiple proteins that inhibit a broad range of inflammatory cell types. We are born with a population of Tregs called natural Tregs. And later in life, new Tregs can be generated by exposure of T cells to TGF-beta and IL-2. These are called induced Tregs or ITregs. The balance of Tregs to T-effectors is critical to maintain health or immune homeostasis. In autoimmune disease, effector T cells turn against specific proteins of the patient's body, resulting in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, type 1 diabetes, lupus, and many others. Tregs are required to control this abnormal T-effector immune response, which causes destruction of healthy tissue. Therapeutics aimed at restoring the balance of Treg and T-effector cells to treat autoimmune disease have not been effective in achieving this balance to date. Through innovative insights into T-cell behavior and breakthrough protein engineering, Q has developed Q401, designed to bind to the destructive autoimmune effector cells, transforming them into anti-inflammatory regulatory Tregs. This results not only in a quite notable increase in the number of stable and functional T-rays, but also reduces the number of disease-causing effector T-cells. The Q401 transformation of the autoimmune response is made possible by enabling simultaneous signaling of the TGF-beta and IL-2 receptors on activated effector T-cells. We believe this is revolutionary technology. With the potential of Q401 to profoundly reverse the inflammatory immune response, we believe new levels of efficacy in multiple autoimmune diseases are possible. We also believe that by returning the patient to immune homeostasis, long-term immune tolerance can occur. In my professional opinion, after overseeing immunology clinical development for over 20 years, I have never before seen a molecule with the potential of Q401 to broadly and effectively transform the treatment of autoimmune disease. I would like to make some important points on slide 11. As you can see from these various scientific journals, TGF-beta, together with IL-2, plays an essential role in the induction of regulatory T cells, which is a critical element of immune homeostasis. With that, it is important to point out that TGF-beta has been extremely challenging to use as a therapeutic. It has not been possible to either combine IL-2 and TGF-beta independently or make a functional single hybrid molecule that contains both proteins. Three main challenges that needed to be addressed are, first, wild type forms of TGF-beta and IL-2 have high potential for off-target toxicity. Second, individual wild type cytokines have very short half-lives. making pharmacology very challenging. And finally, large-scale manufacturing of recombinant TGF-beta has been challenging due to the characteristics of the protein and is frequently toxic to the cell lines used to produce the molecule. Our bispecific biologic candidate, Q401, is the first and only molecule that we know of that successfully combines the activity of TGF-beta and IL-2 into one off-the-shelf molecule, and based on our preclinical studies, appears to have overcome the challenges inherent with TGF-beta and IL-2. I will now describe Q's groundbreaking engineering on this program in the next few slides. Before we present some of our most recent data, I thought I should summarize a few of the key program elements that we will be discussing depicted on slide 12. first q401 is a bispecific molecule composed of two cytokine molecules a modified il-2 and a modified and masked tgf beta both attached to an fc backbone that stabilizes the molecule and prolongs its pharmacokinetics q's novel protein engineering has demonstrated pre-clinically simultaneous and conditional signaling of il-2 and tgf beta in t cells And in doing so, has enabled Q to unlock the potential of TGF-beta and IL-2 signaling cascade. The attenuation of both cytokine molecules, along with the design of the TGF-beta mask, fosters conditional binding and selectivity and enhances the therapeutic window. Importantly, the mask also prevents toxicity of TGF-beta to its own producer cells and has allowed Q to develop a highly productive cell line that has translated into excellent manufacturability. With its unique design and mechanism of action, we have demonstrated therapeutic benefit with Q401 in three distinct autoimmune disease models, in addition to a model of hypersensitivity and inflammation. Q401 has been well tolerated in non-GLP toxicology studies across three species, including non-human primates, at dose levels that result in maximum Treg expansion. We should also point out that several components of Q401 have come from the Q100 series, which has been in the clinic in over 150 patients. We believe this may accelerate some of the development requirements of Q401. This robust data package suggests the potential for a new standard of care in multiple autoimmune indications and requires no HLA restriction. Manufacturing and IND enabling studies are currently underway. The combined signaling of TGF-beta and IL-2 as provided by Q401 and shown here on slide 13 is designed to provide a clear differentiation from the other drugs in this space. Q401 increases both existing Tregs and induces new Tregs or ITregs by transforming autoreactive T cells into induced or ITregs thus reducing the number of inflammatory cells and markedly improving the Treg to T-effector ratio. The simultaneous signaling of both cascades results in a unique effect on activated cells, as shown in the highlighted section. When IL-2 and TGF-beta act together on existing natural Tregs, robust expansion of natural Tregs occurs. The unique additional effect is that when bound to activated effector T cells, the combined signaling induces the transformation of autoreactive T effectors into stable IT regs, as seen in blue. This transformation results in a reduction in the number of the activated effector T cells and a notable increase in both naturally occurring and induced T regs. It is important to note that it has been demonstrated that these induced T regs are highly stable and functionally suppressive. In contrast, Looking at the image on the left, on its own, IL-2 and IL-2 mutines stimulate the expansion of natural T regs as seen in red. The challenge is that these proteins can also promote the expansion of the T effector compartment, thus narrowing the selectivity window and potentially limiting efficacy in autoimmune disease. With the robust increase in two types of Tregs, while transforming and reducing the number of autoreactive cells, we believe immune homeostasis can be restored and treatment with Q401 may result in a transformative clinical benefit. I will now like to turn the call over to Dr. Rich DiPaolo, who is professor and chair of the Department of Molecular Microbiology and Immunology at St. Louis University. Dr. DiPaolo has made significant contributions to the field of regulatory T cells, also referred to as Tregs. Notably, Dr. DiPaolo was among the first to define the in vivo suppressive functions of Tregs in autoimmune settings. He also played a pivotal role in early studies that demonstrated the fundamental importance of concurrent signaling from both TGF-beta and IL-2 in the induction of induced Tregs. Dr. DiPaolo will now review data he has generated with Q401 in his laboratory.